Evaluation of host cellular responses to Epstein–Barr virus (EBV) in adult lung transplant patients with EBV‐associated diseases

Author:

Zaffiri Lorenzo12ORCID,Messinger Joshua E.3,Bush Erika J.2,Staats Janet S.4,Patel Prekshaben4ORCID,Palmer Scott M.2ORCID,Weinhold Kent J.4ORCID,Snyder Laurie D.2ORCID,Luftig Micah A.3ORCID

Affiliation:

1. Division of Pulmonary and Critical Care Cedars‐Sinai Medical Center Los Angeles California USA

2. Division of Pulmonary and Critical Care Duke University Durham North Carolina USA

3. Department of Molecular Genetics and Microbiology Duke University School of Medicine Durham North Carolina USA

4. Department of Surgery Duke University Durham North Carolina USA

Abstract

AbstractEpstein–Barr virus (EBV) reactivation is commonly observed in lung transplant recipients (LTRs). However, cellular immune responses to EBV in adult LTRs have not been well described. We aimed to study CD4/CD8 ratio, EBV‐specific T cells polyfunctional responses and phenotypic changes in natural killer (NK) cells in adult LTRs presenting with EBV‐associated diseases. The CD4/CD8 ratio was significantly decreased in LTRs with EBV DNAemia compared with LTRs without EBV DNAemia and healthy controls (HCs). Stimulation with EBV lytic antigen BZLF1 peptide pools induced significant individual and polyfunctional responses from CD8+CD69+ T cells. Frequencies of CD8+CD69+ T cells expressing CD107a were significantly higher in LTRs without EBV DNAemia than in LTRs with DNAemia. Frequencies of CD8+CD69+ T cells concurrently expressing CD107a, IFN‐γ, and TNF‐α were significantly greater in LTRs with and without EBV DNAemia than in HCs. Finally, BZLF1 induced significantly higher frequencies of CD8+CD69+ T cells expressing CD107a and IFN‐γ in LTRs without EBV DNAemia when compared with EBNA3B. Frequency of more differentiated CD56dimCD16pos NK cells was significantly decreased in LTRs with EBV DNAemia and PTLD compared with HCs. In conclusion, we noted the presence of significant changes in circulating cellular immune responses to EBV in adult LTRs.

Publisher

Wiley

Subject

Infectious Diseases,Virology

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